Fix ins/dups where splice region is preserved

Author: b0d0nne11

src/hgvs/assemblymapper.py

@@ -9,8 +9,12 @@
     HGVSError,
     HGVSInvalidVariantError,
     HGVSUnsupportedOperationError,
+    HGVSInvalidIntervalError,
 )
 from hgvs.variantmapper import VariantMapper
+from hgvs.posedit import PosEdit
+from hgvs.edit import NARefAlt
+from hgvs.location import SimplePosition, Interval
 
 _logger = logging.getLogger(__name__)
 
@@ -172,7 +176,31 @@ def n_to_c(self, var_n):
         return self._maybe_normalize(var_out)
 
     def c_to_p(self, var_c):
-        var_out = super(AssemblyMapper, self).c_to_p(var_c)
+        var_out = super(AssemblyMapper, self)._c_to_p(var_c)
+
+        if (
+            var_c.posedit.edit.type in ['ins', 'dup']
+            and var_c.type in "cnr"
+            and var_c.posedit.pos is not None
+            and (var_c.posedit.pos.start.offset != 0 or var_c.posedit.pos.end.offset != 0)
+            and var_out.posedit is None
+        ):
+            try:
+                var_g = self.c_to_g(var_c)
+                strand = self._fetch_AlignmentMapper(tx_ac=var_c.ac).strand
+
+                for shuffle_direction in [3, 5]:
+                    shifted_var_g = self._far_shift(var_g, shuffle_direction, strand)
+                    shifted_var_c = super(AssemblyMapper, self).g_to_c(
+                        shifted_var_g, var_c.ac, alt_aln_method=self.alt_aln_method
+                    )
+                    var_out = super(AssemblyMapper, self)._c_to_p(shifted_var_c)
+
+                    if var_out.posedit is not None:
+                        break
+            except (HGVSInvalidVariantError, HGVSInvalidIntervalError, HGVSUnsupportedOperationError):
+                pass
+
         return self._maybe_normalize(var_out)
 
     def relevant_transcripts(self, var_g):
@@ -268,6 +296,34 @@ def _maybe_normalize(self, var):
                 # fall through to return unnormalized variant
         return var
 
+    def _far_shift(self, var_g, shuffle_direction, strand):
+        """Attempt to shift a variant all the way left or right. Rewrite
+        duplications as insertions so that the change is shifted as far as
+        possible."""
+        normalizer = hgvs.normalizer.Normalizer(
+            self._norm.hdp, alt_aln_method=self.alt_aln_method, validate=False, shuffle_direction=shuffle_direction
+        )
+        shifted_var_g = normalizer.normalize(var_g)
+        if shifted_var_g.posedit.edit.type == 'dup':
+            self._replace_reference(shifted_var_g)
+            if (strand == 1 and shuffle_direction == 3) or (strand == -1 and shuffle_direction == 5):
+                shifted_var_g.posedit = PosEdit(
+                    pos=Interval(
+                        start=SimplePosition(base=shifted_var_g.posedit.pos.start.base-1),
+                        end=SimplePosition(base=shifted_var_g.posedit.pos.start.base),
+                    ),
+                    edit=NARefAlt(ref=None, alt=shifted_var_g.posedit.edit.ref)
+                )
+            else:
+                shifted_var_g.posedit = PosEdit(
+                    pos=Interval(
+                        start=SimplePosition(base=shifted_var_g.posedit.pos.end.base),
+                        end=SimplePosition(base=shifted_var_g.posedit.pos.end.base+1),
+                    ),
+                    edit=NARefAlt(ref=None, alt=shifted_var_g.posedit.edit.ref)
+                )
+        return shifted_var_g
+
 
 # <LICENSE>
 # Copyright 2018 HGVS Contributors (https://github.com/biocommons/hgvs)

src/hgvs/variantmapper.py

@@ -427,6 +427,21 @@ def c_to_p(self, var_c, pro_ac=None):
 
         """
 
+        var_p = self._c_to_p(var_c, pro_ac=None)
+
+        if (
+            var_c.posedit.edit.type in ['ins', 'dup']
+            and var_c.type in "cnr"
+            and var_c.posedit.pos is not None
+            and (var_c.posedit.pos.start.offset != 0 or var_c.posedit.pos.end.offset != 0)
+            and var_p.posedit is None
+        ):
+            raise HGVSUnsupportedOperationError('c_to_p not supported on VariantMapper for this var_c, try AssemblyMapper')
+
+        return var_p
+
+
+    def _c_to_p(self, var_c, pro_ac=None):
         if not (var_c.type == "c"):
             raise HGVSInvalidVariantError("Expected a cDNA (c.) variant; got " + str(var_c))
         if self._validator:

tests/data/gcp/real.tsv

@@ -58,6 +58,5 @@ ID00056	NC_000010.10:g.89693009delG	NM_000314.4:c.492+1delG	NP_000305.3:p.?
 ID00057	NC_000010.10:g.89711873A>C	NM_000314.4:c.493-2A>C	NP_000305.3:p.?
 ID00058	NC_000010.10:g.89717676G>A	NM_000314.4:c.701G>A	NP_000305.3:p.(Arg234Gln)
 ID00059	NC_000010.10:g.89717777G>A	NM_000314.4:c.801+1G>A	NP_000305.3:p.?
-ID00060	NC_000010.10:g.89720648dupT	NM_000314.4:c.802-3dupT	NP_000305.3:p.?
 ID00061	NC_000005.9:g.131705667G>T	NM_003060.3:c.3G>T	NP_003051.1:p.Met1?
 ID00062	NC_000005.9:g.131706014G>A	NM_003060.3:c.350G>A	NP_003051.1:p.(Trp117*)

tests/issues/test_714.py

@@ -0,0 +1,66 @@
+import os
+
+import hgvs
+import pytest
+from support import CACHE
+
+cases = [
+    {
+        "name": "ins with splice region preserved",
+        "var_c": "NM_004119.2:c.1837+21_1837+22insCGAGAGAATATGAATATGATCTCAAATGGGAGTTTCCAAGAGAAAATTTAGAGTTTGGTAAGAATGGAATGTGCCAAA",
+        "var_p": "NP_004110.2:p.(Lys614_Val615insAsnGlyMetCysGlnThrArgGluTyrGluTyrAspLeuLysTrpGluPheProArgGluAsnLeuGluPheGlyLys)"
+    },
+    {
+        "name": "dup with splice region preserved",
+        "var_c": "NM_004119.2:c.1835_1837+3dup",
+        "var_p": "NP_004110.2:p.(Gly613_Lys614insIleGly)"
+    },
+    {
+        "name": "dup with splice region preserved",
+        "var_c": "NM_005228.4:c.2284-5_2290dup",
+        "var_p": "NP_005219.2:p.(Ala763_Tyr764insPheGlnGluAla)"
+    },
+    {
+        "name": "dup with splice region preserved",
+        "var_c": "NM_004456.4:c.2196-1_2196dup",
+        "var_p": "NP_004447.2:p.(Tyr733AspfsTer8)"
+    },
+    {
+        "name": "dup with splice region preserved",
+        "var_c": "NM_016222.3:c.27+2_27+5dup",
+        "var_p": "NP_057306.2:p.(Arg10ValfsTer20)"
+    },
+    {
+        "name": "dup with splice region preserved",
+        "var_c": "NM_182758.2:c.2953-31_2953-26dup",
+        "var_p": "NP_877435.2:p.?"
+    },
+    {
+        "name": "dup with broken cigar mapping",
+        "var_c": "NM_000267.3:c.8315-290_8457dup",
+        "var_p": "NP_000258.1:p.?"
+    }
+]
+
+
+@pytest.fixture(scope="module")
+def hp():
+    return hgvs.parser.Parser()
+
+
+@pytest.fixture(scope="module")
+def hdp():
+    return hgvs.dataproviders.uta.connect(
+        mode=os.environ.get("HGVS_CACHE_MODE", "run"), cache=CACHE
+    )
+
+
+@pytest.fixture(scope="module")
+def am37(hdp):
+    return hgvs.assemblymapper.AssemblyMapper(hdp, assembly_name="GRCh37")
+
+
+@pytest.mark.parametrize("case", cases)
+def test_real_c_to_p(case, hp, am37):
+    var_c = hp.parse(case["var_c"])
+    assert str(am37.c_to_p(var_c)) == case["var_p"]

tests/support/mock_input_source.py

@@ -53,6 +53,9 @@ def get_tx_seq(self, ac):
     def get_seq(self, ac, start_i=None, end_i=None):
         return self.get_tx_seq(ac)[start_i:end_i]
 
+    def get_pro_ac_for_tx_ac(self, ac):
+        return 'MOCK'
+
     #
     # internal methods
     #